W. B. Saunders Company: West Washington Square Philadelphia, PA 19 105 1 St. Anne's Road Eastbourne, East Sussex BN21 3 U N , England Second Edition 1 Goldthorne Avenue Toronto, Ontario M8Z 5T9, Canada THE CELL Apartado 26370 -Cedro 5 12 Mexico 4. D.F.. Mexico Rua Coronel Cabrita, 8 Sao Cristovao Caixa Postal 21 176 Rio de Janeiro, Brazil 9 Waltham Street Artarmon, N. S. W. 2064, Australia Ichibancho, Central Bldg., 22-1 Ichibancho Chiyoda-Ku, Tokyo 102, Japan Library of Congress Cataloging in Publication Data Fawcett, Don Wayne, 1917The cell. DON W . FAWCETT. M.D. Hersey Professor of Anatomy Harvard Medical School Edition of 1966 published under title: An atlas of fine structure. Includes bibliographical references. 2. Ultrastructure (Biology)1. Cytology -Atlases. I. Title. [DNLM: 1. Cells- UltrastructureAtlases. 2. Cells- Physiology - Atlases. QH582 F278c] Atlases. QH582.F38 1981 591.8'7 80-50297 ISBN 0-7216-3584-9 Listed here is the latest translated edition of this book together with the language of the translation and the publisher. German (1st Edition)- Urban and Schwarzenberg, Munich, Germany ISBN The Cell W. B. SAUNDERS COMPANY Philadelphia London Toronto Mexico City Rio de Janeiro Sydney Tokyo 0-7216-3584-9 © 1981 by W. B. Saunders Company. Copyright 1966 by W. B. Saunders Company. Copyright under the Uniform Copyright Convention. Simultaneously published in Canada. All rights reserved. This book is protected by copyright. N o part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Made in the United States of America. Press of W. B. Saunders Company. Library of Congress catalog card number 80-50297. Last digit is the print number: 9 8 7 6 5 4 3 2 CONTRIBUTORS OF ELECTRON MICROGRAPHS Dr. John Albright Dr. David Albertini Dr. Nancy Alexander Dr. Winston Anderson Dr. Jacques Auber Dr. Baccio Baccetti Dr. Michael Barrett Dr. Dorothy Bainton Dr. David Begg Dr. Olaf Behnke Dr. Michael Berns Dr. Lester Binder Dr. K. Blinzinger Dr. Gunter Blobel Dr. Robert Bolender Dr. Aiden Breathnach Dr. Susan Brown Dr. Ruth Bulger Dr. Breck Byers Dr. Hektor Chemes Dr. Kent Christensen Dr. Eugene Copeland Dr. Romano Dallai Dr. Jacob Davidowitz Dr. Walter Davis Dr. Igor Dawid Dr. Martin Dym Dr. Edward Eddy Dr. Peter Elias Dr. A. C. Faberge Dr. Dariush Fahimi Dr. Wolf Fahrenbach Dr. Marilyn Farquhar Dr. Don Fawcett Dr. Richard Folliot Dr. Michael Forbes Dr. Werner Franke Dr. Daniel Friend Dr. Keigi Fujiwara Dr. Penelope Gaddum-Rosse Dr. Joseph Gall Dr. Lawrence Gerace Dr. Ian Gibbon Dr. Norton Gilula Dr. Jean Gouranton Dr. Kiyoshi Hama Dr. Joseph Harb Dr. Etienne de Harven Dr. Elizabeth Hay Dr. Paul Heidger Dr. Arthur Hertig Dr. Marian Hicks Dr. Dixon Hingson Dr. Anita Hoffer Dr. Bessie Huang Dr. Barbara Hull Dr. Richard Hynes Dr. Atsuchi Ichikawa Dr. Susumu It0 Dr. Roy Jones Dr. Arvi Kahri Dr. Vitauts Kalnins Dr. Marvin Kalt Dr. Taku Kanaseki Dr. Shuichi Karasaki Dr. Morris Karnovsky Dr. Richard Kessel Dr. Toichiro Kuwabara Dr. Ulrich Laemmli Dr. Nancy Lane Dr. Elias Lazarides Dr. Gordon Leedale Dr. Arthur Like Dr. Richard Linck Dr. John Long Dr. Linda Malick Dr. William Massover Dr. A. Gideon Matoltsy Dr. Scott McNutt Dr. Oscar Miller Dr. Mark Mooseker Dr. Enrico Mugnaini Dr. Toichiro Nagano Dr. Marian Neutra Dr. Eldon Newcomb Dr. Ada Olins Dr. Gary Olson Dr. Jan Orenstein Dr. George Palade Dr. Sanford Palay Dr. James Paulson Dr. Lee Peachey Dr. David Phillips Dr. Dorothy Pitelka Dr. Thomas Pollard Dr. Keith Porter iv Dr. Jeffrey Pudney Dr. Eli0 Raviola Dr. Giuseppina Raviola Dr. Janardan Reddy Dr. Thomas Reese Dr. Jean Revel Dr. Hans Ris Dr. Joel Rosenbaum Dr. Evans Roth Dr. Thomas Roth Dr. Kogaku Saito Dr. Peter Satir .111 .. CONTRIBUTORS OF PHOTOMICROGRAPHS Dr. Dr. Dr. Dr. Dr. Dr. Dr. Dr. Dr. Dr. Dr. Dr. Manfred Schliwa Nicholas Severs Emma Shelton Nicholai Simionescu David Smith Andrew Somlyo Sergei Sorokin Robert Specian Andrew Staehelin Fumi Suzuki Hewson Swift George Szabo Dr. John Tersakis Dr. Guy de Th6 Dr. Lewis Tilney Dr. Greta Tyson Dr. Wayne Vogl Dr. Fred Warner Dr. Melvyn Weinstock Dr. Richard Wood Dr. Raymond Wuerker Dr. Eichi Yamada PREFACE PREFACE ably used in combination with biochemical, biophysical, and immunocytochemical techniques. Its use has become routine and one begins to detect a decline in the number and quality of published micrographs as other analytical methods increasingly capture the interest of investigators. Although purely descriptive electron microscopic studies now yield diminishing returns, a detailed knowledge of the structural organization of cells continues to be an indispensable foundation for research on cell biology. In undertaking this second edition I have been motivated by a desire to assemble and make easily accessible to students and teachers some of the best of the many informative and aesthetically pleasing transmission and scanning electron micrographs that form the basis of our present understanding of cell structure. The historical approach employed in the text may not be welcomed by all. In the competitive arena of biological research today investigators tend to be interested only in the current state of knowledge and care little about the steps by which we have arrived at our present position. But to those of us who for the past 25 years have been privileged to participate in one of the most exciting and fruitful periods in the long history of morphology, the young seem to be entering the theater in the middle of an absorbing motion picture without knowing what has gone before. Therefore, in the introduction to each organelle, I have tried to identify, in temporal sequence, a few of the major contributors to our present understanding of its structure and function. In venturing to do this I am cognizant of the hazards inherent in making judgments of priority and significance while many of the dramatis personae are still living. My apologies to any who may feel that their work has not received appropriate recognition. It is my hope that for students and young investigators entering the field, this book will provide a useful introduction to the architecture of cells and for teachers of cell biology a guide to the literature and a convenient source of illustrative material. The sectional bibliographies include references to many reviews and research papers that are not cited in the text. It is believed that these will prove useful to those readers who wish to go into the subject more deeply. The omission of magnifications for each of the micrographs will no doubt draw some criticism. Their inclusion was impractical since the original negatives often remained in the hands of the contributing microscopists and micrographs submitted were cropped or copies enlarged to achieve pleasing composition and to focus the reader's attention upon the particular organelle under discussion. Absence was considered preferable to inaccuracy in stated magnification. The majority of readers, I believe, will be interested in form rather than measurement and will not miss this datum. Assembling these micrographs illustrating the remarkable order and functional design in the structure of cells has been a satisfying experience. I am indebted to more than a hundred cell biologists in this country and abroad who have generously responded to my requests for exceptional micrographs. It is a source of pride that nearly half of the contributors were students, fellows or colleagues in the Department of Anatomy at Harvard Medical School at some time in the past 20 years. I am grateful for their stimulation and for their generosity in sharing prints and negatives. It is a pleasure to express my appreciation for the forbearance of my wife who has had to communicate with me through the door of the darkroom for much of the year while I printed the several hundred micrographs; and for the patience of Helen Deacon who has typed and retyped the manuscript; for the skill of Peter Ley, who has made many copy negatives to gain contrast with minimal loss of detail; and for the artistry of Sylvia Collard Keene whose drawings embellish the text. Special thanks go to Elio and Giuseppina Raviola who read the manuscript and offered many constructive suggestions; and to Albert Meier and the editorial and production staff of the W. B. Saunders Company, the publishers. And finally I express my gratitude to the Simon Guggenheim Foundation whose commendable policy of encouraging the creativity of the young was relaxed to support my efforts during the later stages of preparation of this work. The history of morphological science is in large measure a chronicle of the discovery of new preparative techniques and the development of more powerful optical instruments. In the middle of the 19th century, improvements in the correction of lenses for the light microscope and the introduction of aniline dyes for selective staining of tissue components ushered in a period of rapid discovery that laid the foundations of modern histology and histopathology. The decade around the turn of this century was a golden period in the history of microscopic anatomy, with the leading laboratories using a great variety of fixatives and combinations of dyes to produce histological preparations of exceptional quality. The literature of that period abounds in classical descriptions of tissue structure illustrated by exquisite lithographs. In the decades that followed, the tempo of discovery with the light microscope slackened; interest in innovation in microtechnique declined, and specimen preparation narrowed to a monotonous routine of paraffin sections stained with hematoxylin and eosin. In the middle of the 20th century, the introduction of the electron microscope suddenly provided access to a vast area of biological structure that had previously been beyond the reach of the compound microscope. Entirely new methods of specimen preparation were required to exploit the resolving power of this new instrument. Once again improvement of fixation, staining, and microtomy commanded the attention of the leading laboratories. Study of the substructure of cells was eagerly pursued with the same excitement and anticipation that attend the geographical exploration of a new continent. Every organ examined yielded a rich reward of new structural information. Unfamiliar cell organelles and inclusions and new macromolecular components of protoplasm were rapidly described and their function almost as quickly established. This bountiful harvest of new structural information brought about an unprecedented convergence of the interests of morphologists, physiologists, and biochemists; this convergence has culminated in the unified new field of science called cell biology. The first edition of this book (1966) appeared in a period of generous support of science, when scores of laboratories were acquiring electron microscopes and hundreds of investigators were eagerly turning to this instrument to extend their research to the subcellular level. A t that time, an extensive text in this rapidly advancing field would have been premature, but there did seem to be a need for an atlas of the ultrastructure of cells to establish acceptable technical standards of electron microscopy and to define and illustrate the cell organelles in a manner that would help novices in the field to interpret their own micrographs. There is reason to believe that the first edition of The Cell: An Atlas of Fine Structure fulfilled this limited objective. In the 14 years since its publication, dramatic progress has been made in both the morphological and functional aspects of cell biology. The scanning electron microscope and the freeze-fracturing technique have been added to the armamentarium of the miscroscopist, and it seems timely to update the book to incorporate examples of the application of these newer methods, and to correct earlier interpretations that have not withstood the test of time. The text has been completely rewritten and considerably expanded. Drawings and diagrams have been added as text figures. A few of the original transmission electron micrographs to which I have a sentimental attachment have been retained, but the great majority of the micrographs in this edition are new. These changes have inevitably added considerably to the length of the book and therefore to its price, but I hope these will be offset to some extent by its greater informational content. Twenty years ago, the electron microscope was a solo instrument played by a few virtuosos. Now it is but one among many valuable research tools, and it is most profitv D ON W. FAWCETT Boston, Massachusetts CONTENTS CONTENTS MITOCHONDRIA ................................................................................. 410 CELL SURFACE................................................................................... 1 Cell Membrane ........................................................................................ Glycocalyx or Surface Coat ....................................................................... Basal Lamina .......................................................................................... 1 35 45 SPECIALIZATIONS O F T H E FREE SURFACE .................................... 65 Specializations for Surface Amplification...................................................... Relatively Stable Surface Specializations ...................................................... Specializations Involved in Endocytosis ....................................................... 68 80 92 ...................................................... Tight Junction (Zonula Occludens).............................................................. Adhering Junction (Zonula Adherens).......................................................... Sertoli Cell Junctions ................................................................................ Zonula Continua and Septate Junctions of Invertebrates ................................. Desmosomes ........................................................................................... Gap Junctions (Nexuses)........................................................................... Intercalated Discs and Gap Junctions of Cardiac Muscle ................................ 124 ............................................................................................ Nuclear Size and Shape ............................................................................ Chromatin............................................................................................... Mitotic Chromosomes ............................................................................... Nucleolus ............................................................................................... Nucleolar Envelope .................................................................................. Annulate Lamellae ................................................................................... 195 ENDOPLASMIC RETICULUM ............................................................. 303 JUNCTIONAL SPECIALIZATIONS NUCLEUS Structure of Mitochondria .......................................................................... Matrix Granules ...................................................................................... Mitochondria1 DNA and RNA ................................................................... Division of Mitochondria ........................................................................... Fusion of Mitochondria ............................................................................. Variations in Internal Structure .................................................................. Mitochondria1 Inclusions ........................................................................... Numbers and Distribution ......................................................................... 414 420 424 430 438 442 464 468 LYSOSOMES ......................................................................................... 487 Multivesicular Bodies ............................................................................... 510 PEROXISOMES ..................................................................................... 515 LIPOCHROME PIGMENT .................................................................... 529 MELANIN PIGMENT ........................................................................... 537 CENTRIOLES ....................................................................................... 551 128 129 136 148 156 169 187 Centriolar Adjunct ................................................................................... 568 CILIA AND FLAGELLA ...................................................................... 575 Matrix Components of Cilia ....................................................................... 588 Aberrant Solitary Cilia .............................................................................. 594 Modified Cilia.......................................................................................... 596 Stereocilia ............................................................................................... 598 197 204 226 243 266 292 SPERM FLAGELLUM .......................................................................... 604 Mammalian Sperm Flagellum ..................................................................... 604 Urodele Sperm Flagellum .......................................................................... 619 Insect Sperm Flagellum............................................................................. 624 CYTOPLASMIC INCLUSIONS ............................................................. 641 Glycogen ................................................................................................ Lipid ...................................................................................................... Crystalline Inclusions ............................................................................... Secretory Products ................................................................................... Synapses ................................................................................................ Rough Endoplasmic Reticulum ................................................................... 303 Smooth Endoplasmic Reticulum ................................................................. 330 Sarcoplasmic Reticulum ............................................................................ 353 GOLGI APPARATUS ............................................................................ 369 Role in Secretion ..................................................................................... 372 Role in Carbohydrate and Glycoprotein Synthesis ......................................... 376 Contributions to the Cell Membrane............................................................ 406 641 655 668 691 722 CYTOPLASMIC MATRIX AND CYTOSKELETON .............................. 743 vii Microtubules ........................................................................................... 743 Cytoplasmic Filaments .............................................................................. 784 PEROXISOMES In an early electron microscopic study of the kidney, Rhodin (1954) described membrane-limited, spherical cytoplasmic particles 0.2 to 0.4 pm in diameter that did not correspond to any of the traditional cell organelles. For lack of a better term, they were called microbodies. Similar structures were soon observed in hepatic cells, but in addition to a homogeneous, finely granular matrix these also contained an inclusion termed the nucleoid, which in some planes of section exhibited a lamellar substructure (Gansler and Rouiller, 1956). Noting that microbodies were more abundant in regenerating liver, Rouiller and Bernhard (1956) considered it likely that they represented formative stages of mitochondria and that the parallel striations in the nucleoid might be precursors of the cristae, but this interpretation gained little support. In their studies on lysosomes, DeDuve and his coworkers developed centrifugation procedures with improved resolving power and were able to separate from the lysosome fraction particles that lacked the typical acid hydrolases but were rich in d-aminoacid oxidase and catalase. It was recognized that this new class of cytoplasmic particles probably corresponded to the "microbodies" previously described by microscopists. It was suggested that the term peroxisome was more appropriate for an organelle in which two hydrogen peroxide-generating enzymes were associated with catalase. This rapidly became the preferred term. Correspondence of DeDuve's peroxisomes to microbodies was soon validated by the demonstration that the ultrastructure of the nucleoid in the microbody was identical to that of crystalline uricase (Hruban and Swift, 1964) and the finding that birds, reptiles, and man - all of which are known to lack uricase - also lack nucleoids in their hepatic microbodies (Afzelius, 1965). The nucleoids of rat hepatic microbodies were then isolated in a high degree of purity and urate oxidase was the only enzymatic activity detected. The isolated nucleoids consisted of parallel bundles of thick-walled, hollow tubules (15 nm outside diameter, 5 nm inside diameter). These were precisely arranged in a repeating pattern throughout the crystalline lattice with 10 such tubules around longitudinal channels 20 nm in diameter. Thus in transverse sections the nucleoids had a honeycomb pattern, and in longitudinal sections they presented an array of alternating dark and light striations (Tsukada et al., 1966). This structure applies only to the rat. The nucleoids of other species have a different organization. Investigation of the origin of peroxisomes has been considerably facilitated by the availability of experimental methods for inducing their proliferation and by a cytochemical reaction for detecting their enzymatic activity. Administration of various hypocholesterolemic drugs results in a rapid increase in hepatic microbodies (Hruban et al., 1970; Diagrammatic reconstruction of the three-dimensional form of the nucleoid in rat hepatic peroxisomes. (From Tsukada et a]., J. Cell Biol. 28:449-460, 1966.) 5 16 PEROXISOMES Reddy and Krishnahantha, 1975), and they can be intensely and selectively stained with the diaminobenzidene reaction for peroxidase (Fahimi, 1968). Despite the specificity of this method and the clarity of the resulting electron micrographs, the origin of peroxisomes remains a subject of controversy. Some investigators insist that their membrane is often continuous at some point with that of the smooth endoplasmic reticulum and that peroxisomes arise as evaginations from that organelle (Novikoff and Shin, 1964; Essner, 1967). Others find no convincing evidence of continuity and suggest instead that new peroxisomes arise from preexisting peroxisomes by a process of budding. Catalase is believed to be synthesized on ribosomes and transferred directly to the peroxisomes without involvement of the reticulum and Golgi complex (Legg and Wood, 1970). Others observe catalase reaction product on ribosomes in the vicinity of weakly stained, small peroxisome-like bodies that lack a distinct limiting membrane, and suggest that catalase which is synthesized on free and bound ribosomes accumulates locally and is then segregated by development of a limiting membrane (Fahimi, 1971). Additional support for the concept of synthesis of peroxisomal enzymes in the cytoplasmic matrix also comes from biochemical studies which indicate that a catalase precursor is discharged into the cytosol and subsequently transferred to the peroxisomes (Lazarow and DeDuve, 1973). Catalase has been localized on free ribosomes but not on membrane-bound ribosomes. Thus it is the prevailing view that uricase and catalase are transferred to the interior of the peroxisome by a posttranslational mechanism (Goldman and Blobel, 1978). The origin of the limiting membrane is not clear, but budding from the rough reticulum or from GERL remains a likely possibility. Application of the cytochemical staining reaction for peroxidase has shown that, in addition to the peroxisomes of kidney and liver, there are very large numbers of small membrane-bounded particles 0.15 to 0.25 urn in the absorptive cells of the intestine and in many other epithelia. Their membranes were originally reported by Novikoff-and coworkers to be continuous with those of the smooth endoplasmic reticulum and they were considered to be local diverticula or varicosities of the reticulum. Owing to their small size and lack of nucleoids, it was suggested that these diminutive peroxidasepositive bodies should be designated microperoxisomes (Novikoff and Novikoff, 1972). Other workers have confirmed their widespread occurrence, but in the absence of reaction product in the lumen of the reticulum, their interpretation as local evaginations of the reticulum has not gained general acceptance. It is clear that peroxisomes occur in a broad spectrum of different sizes, with nucleoids present in some cell types and lacking in others. As in the case of lysosomes, their positive identification cannot be made on morphological criteria alone but requires histochemical demonstration of one or more of their constitutent enzymes. Their functional significance in the metabolism of cells remains obscure. Peroxisomes are abundant in hepatic cells and were first isolated from the crude lysosome fraction of liver homogenates. The micrographs on the facing page show their characteristic appearance in situ (at arrows). They are generally spherical or ovoid and have a homogeneous content of relatively low density. In the rat they usually have a single crystalloid inclusion called the nucleoid. A nucleoid is also present in the hamster but is a thin sheet, with a linear profile in section. Not infrequently it is folded and presents a C or V shape profile in sections. The nucleoid consists of urate oxidase. When present, the nucleoid is helpful in distinguishing peroxisomes from primary lysosomes, but in some species that have no urate oxidase, the nucleoid is absent. In those species in which nucleoids are present in the hepatic peroxisomes, they may be absent in the peroxisomes of other organs. Figure 280. An area of cytoplasm from a rat liver cell containing peroxisomes. (Micrograph courtesy of Robert Bolender.) Figure 281. A comparable micrograph from hamster liver. Figure 280, upper Figure 281, lower 5 17 518 PEROXISOMES Representative examples of microbodies or peroxisomes are shown here at higher magnification. The plane of section may not include the nucleoid, as in the one at the top of the figure. The great majority of nucleoids are sectioned obliquely and show only a faint longitudinal striation. With patient examination of scores of micrographs, rare longitudinal and transverse sections can be found. In this way the lattice of the urate oxidase crystal in the rat peroxisome has been worked out in considerable detail. Figure 282. Rat liver peroxisomes. (Micrograph courtesy of Daniel Friend.) Figure 283. Rat liver peroxisome. (Micrograph courtesy of Richard Wood.) Figure 282, upper Figure 283, lower 5 19 PEROXISOMES Some cell types may contain lysosomes and peroxisomes. In routine preparations, these may be similar in size and density. But when stained with the diaminobenzidene reaction for peroxidase activity, the dense reaction product clearly distinguishes the peroxisomes from the lysosomes. Figures 284 and 285. Leydig cells from boar testis stained with the cytochemical reaction for peroxidase. Figure 284, upper Figure 285, lower 521 PEROXISOMES Although the function of peroxisomes is poorly understood, they appear to be especially abundant in cells involved in cholesterol metabolism and synthesis of steroids - liver, adrenal, ovary, and interstitium of the testis. A relationship to cholesterol metabolism is suggested by the observation that the number of hepatic peroxisomes is dramatically increased by administration of several unrelated hypocholesterolemic drugs. The upper micrograph on the facing page from normal rat liver stained with the diaminobenzidene reaction illustrates the normal size and number of peroxisomes. The lower micrograph shows the remarkable increase after the administration of [4-chloro6-(2.3-xylidine) 2-pyrimidinylthio] acetic acid (Wy-14643). Figure 286. Peroxidase-stained liver cytoplasm. (Micrograph courtesy of Darius Fahimi.) Figure 287. Peroxidase stain of liver from an animal treated with Wy-14643. (Micrograph courtesy of Janardan Reddy, from Reddy and Krishnahantha, Science 190 787-789, 1975.) Figure 286, upper Figure 287, lower PEROXISOMES Peroxisomes (microbodies), first observed in cells of the mouse proximal convoluted tubule, were described as spherical bodies with a homogeneous, finely granular matrix. Nucleoids were not a characteristic feature of those peroxisomes. More recent investigations of comparable organelles in the rat distinguish two types of formed structures in their matrix-cylindrical inclusions 85 to 140 nm in diameter and large tabular crystals varying in thickness and ranging up to 3 pm in length. Some contain mainly crystalline inclusions, some mainly cylinders, and others contain both. The inclusions tend to be at the periphery, and where they are crystals, they tend to deform the organelle into geometric shapes. The accompanying micrograph of a cell from the proximal convoluted tubule shows a peroxisome near the cell base containing both crystals and a few circular profiles of cylinders in cross section. Despite their unusual appearance, these organelles can be identified as peroxisomes by positive staining for catalase and a negative reaction for acid phosphatase. Figure 288. Proximal convoluted tubule cell from rat. (Micrograph courtesy of Michael Barrett and Paul Heidger, from Cell and Tissue 157:283-305, 1975.) Figure 288 PEROXISOMES Two additional examples of peroxisomes from the proximal convoluted tubule of rat kidney, one containing only crystals and the other containing cylindrical inclusions seen here in transverse section. Figures 289 and 290. Peroxisomes from the proximal convoluted tubule of rat kidney. (Micrograph courtesy of Michael Barrett and Paul Heidger, from Cell and Tissue 157:283-305, 1975.) Figure 289, upper Figure 290, lower PEROXISOMES REFERENCES Peroxisomes Afzelius, B. The occurrence and structure of microbodies. A comparative study. J. Cell Biol. 265435-843, 1965. Barrett, J. M. and P. M. Heidger. Microbodies of the rat renal proximal convoluted tubule: Ultrastructural and cytochemical investigations. Cell Tissue Res. 157:283-305, 1975. DeDuve, C. The peroxisome: A new cytoplasmic organelle. Proc. Roy. Soc. Lond. 173:71, 1969. DeDuve, C. and P. Baudhuin. Peroxisomes (microbodies and related particles). Physiol. Rev. 46:323-357, 1966. (Review) DeDuve, C., H. Beaufay, P. Jacques, Y. Rahman-Li, 0. Z. Sellinger, R. Wattiaux and S. DeConnick. Intracellular localization of catalase and of some oxidases in rat liver. Biochim. Biophys. Acta 40: 186-187, 1960. Essner, E. Endoplasmic reticulum and the origin of microbodies in fetal mouse liver. Lab. Invest. 17:71, 1967. Fahimi, H. D. Cytochemical localization of peroxidase activity in rat hepatic microbodies. J. Histochem. Cytochem. 16547-550, 1968. Fahimi, H. D. Morphogenesis of peroxisomes in rat liver. J. Cell Biol. 87A, 1971. Gansler, H. and C. Rouiller. Modifications physiologiques et pathologiques du chondrome. Etude an microscope klectronique. Schweitz Z. Pathol. Bakt. 19:217-243, 1956. Goldman, B. M. and G . Blobel. Biogenesis of peroxisomes: Intracellular site of synthesis of catalase and uricase. Proc. Nat. Acad. Sci. 753066-5070, 1978. Hruban, Z. and M. Rechigl. Microbodies and related particles. Int. Rev. Cytol. Suppl. 1, 1969. (Review) Hruban, Z., E . L. Vigil, A. Slesers and E. Hopkins. Microbodies. Constituent organelles of animal cells. Lab. Invest. 27:184-191, 1972. (Review) Hruban, Z. and H. Swift. Uricase: Localization in hepatic microbodies. Science 146:1316-1317, 1964. Hruban, Z., Y. Mochizuki, J. R. Esterly and T. W. Wong. Some effects of hypocholesterolemic and related agents. Fed. Proc. 29:385, 1970. Lazarow, P. P. and C. DeDuve. The synthesis and turnover of rat liver peroxisomes. V. Intracellular pathway of catalase synthesis. J . Cell Biol. 59507-524, 1973. Legg, P. G. and R. L. Wood. New observations on microbodies. A cytochemical study on CPlB-treated rat liver. J. Cell Biol. 45:118-129, 1970. Leighton, F., B. Poole, H. Beaufay et al. Large scale separation of peroxisomes, mitochondria, and lysosomes from the liver of rats injected with Triton WR-1339. J. Cell Biol. 37:483-513, 1968. Novikoff, P. M. and A. B. Novikoff. Peroxisomes in absorptive cells of mammalian small intestine. J. Cell Biol. 53532-560, 1972. Reddy, J. K. and T. P. Krishnahantha. Hepatic peroxisome proliferation: Induction by two novel compounds structurally unrelated to chlofibrate. Science 190:787-789, 1975. Rhodin, J. Correlation of ultrastructural organization and function in normal and experimentally changed proximal convoluted tubule cells of mouse kidney. A. B. Godvil, Stockholm, 1954. Rouiller, C. and W. Bernhard. "Microbodies" and the problem of mitochondria1 regeneration in liver cells. J . Biophys. Biochem. Cytol. 2:Suppl. 355-360, 1956. Shmitka, T. K. Comparative ultrastructure of hepatic microbodies in some mammals and birds in relation to species differences in uricase activity. J. Ultrastr. Res. 16598, 1966. Svaboda, D. J . and D. L. Azarnoff. Response of hepatic microbodies to a hypolipidemic agent ethyl chlorophenoxyisobutyrate (CPIB). J. Cell Biol. 30:442-450, 1966. Tsukada, T., Y. Mochizuki and S. Fujiwara. The nucleoids of rat liver cell microbodies. J. Cell Biol. 28:449-460, 1966. '